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Background The Hawthorne Effect occurs when participants alter their behavior when they are aware that they are being examined. The effect has been reported in many experiments, including gait analysis, and is considered an important source of bias that might impact both clinical and research results. Cognitive distraction is one potential solution to reducing the Hawthorne effect during gait analysis, but it is challenging in children, and can, in itself, alter gait. This study investigated the carryover effect of an alternative low-immersion avatar-based intervention on gait and subjective feelings in typically developing children. Research Question Will a low-immersion avatar-based intervention change feelings and indicators of temporospatial and kinematic outcomes in children in a laboratory setting, potentially reducing the Hawthorne Effect? Methods Typically developing children aged 5–13 participated in a standard laboratory gait analysis before experiencing a game in which they viewed their motion on monitors around the lab as that of a cartoon avatar in a 3D virtual environment. Following this intervention, standard walking trials were repeated. In addition, participants completed a survey of their feelings about the study both before onset and after completion. Results Thirty-one children participated in the study, 16 females and 15 males, mean aged 9.1 years. Arm swing, proposed as a measure of how relaxed and natural gait was, increased significantly following the intervention, while temporospatial parameters did not. The effect was more pronounced in females and younger children. Participants felt significantly happier, more excited, less scared, and less sad after the intervention. Changes in feelings were not closely associated with changes in gait. Significance This study suggests that gamification may reduce the Hawthorne effect and potentially produce more natural gait in children. The game intervention had a carryover effect, producing changes in gait even after the intervention was removed.

Statistical analyses of randomized controlled trials (RCTs) yield a causally valid estimate of the overall treatment effect, which is the contrast between the outcomes in two randomized treatment groups commonly accompanied by a confidence interval. In addition, the trial investigators may want to examine whether the observed treatment effect varies across patient subgroups (also called 'heterogeneity of treatment effects'), i.e. whether the treatment effect is modified by the value of a variable assessed at baseline. The statistical approach for this evaluation of potential effect modifiers is a test for statistical interaction to evaluate whether the treatment effect varies across levels of the effect modifier. In this article, we provide a concise and nontechnical explanation of the use of simple statistical tests for interaction to identify effect modifiers in RCTs. We explain how to calculate the test of interaction by hand, applied to a dataset with simulated data on 1,000 imaginary participants for illustration. (C) 2021 The Author(s). Published by Elsevier Inc.

We aimed to assess whether high-density lipoprotein (HDL) cholesterol modifies the association between adiponectin and incident cardiovascular (CV) morbidity and mortality in Type 2 Diabetes Mellitus (T2DM) and vice versa. At baseline, 106 T2DM participants with various degrees of renal function were enrolled and followed up over a period of 7 years with fatal/nonfatal CV events as outcome. During the follow-up, 49 participants experienced incident CV events (28 fatal, 21 nonfatal). On univariate Fine and Gray sub-hazard models, HDL cholesterol was a strong modifier of the association between adiponectin and CV outcomes both on crude (P = 0.011) and gender- and eGFR-adjusted models (P = 0.010). The protective effect for CV events portended by a fixed increase in adiponectin (1 μg/ml) was progressively higher across increasing values of HDL cholesterol. Moreover, plasma adiponectin also modified the protective effect of HDL on CV outcomes both in crude and multivariate analyses. We found a mutual effect modification between adiponectin and HDL as risk factors of CV events in participants with T2DM. Our results are coherent with the hypothesis that HDL cholesterol might play a pivotal role in the interpretation of the association between adiponectin and the risk of adverse CV outcomes in this population.

Age-at-onset (AAO) affects psychiatric disorder outcome; substance (SUDs) or alcohol use disorders (AUDs) may influence their onset. Affective temperaments may affect early AAO and drug-use proneness.

A surprising feature of the SARS-CoV-2 pandemic to date is the low burdens reported in sub-Saharan Africa (SSA) countries relative to other global regions. Potential explanations (e.g., warmer environments1, younger populations2–4) have yet to be framed within a comprehensive analysis accounting for factors that may offset the effects of climate and demography. Here, we synthesize factors hypothesized to shape the pace of this pandemic and its burden as it moves across SSA, encompassing demographic, comorbidity, climatic, healthcare and intervention capacity, and human mobility dimensions of risk. We find large scale diversity in probable drivers, such that outcomes are likely to be highly variable among SSA countries. While simulation shows that extensive climatic variation among SSA population centers has little effect on early outbreak trajectories, heterogeneity in connectivity is likely to play a large role in shaping the pace of viral spread. The prolonged, asynchronous outbreaks expected in weakly connected settings may result in extended stress to health systems. In addition, the observed variability in comorbidities and access to care will likely modulate the severity of infection: We show that even small shifts in the infection fatality ratio towards younger ages, which are likely in high risk settings, can eliminate the protective effect of younger populations. We highlight countries with elevated risk of ‘slow pace’, high burden outbreaks. Empirical data on the spatial extent of outbreaks within SSA countries, their patterns in severity over age, and the relationship between epidemic pace and health system disruptions are urgently needed to guide efforts to mitigate the high burden scenarios explored here.

Prehabilitation is a new field of research that aims to optimize modifiable surgical risk factors before surgery to improve patient-oriented outcomes preoperatively and postoperatively. As with any new intervention, the pressing questions that arise include what interventions work, for whom they work, and when do they work best? Given that prehabilitation can be resource intensive, and that preoperative patient characteristics are likely to produce variation in response to treatment, establishing answers to these questions is critical for successful implementation of prehabilitation in clinical practice. The objective of this review article is to describe the illuminating potential of including "third-variable effects" into the integration of research design; by planning for and including measurements of mediators, moderators, and confounders in the design and analysis of prehabilitation research, we can begin to answer practical, clinically relevant questions.

The beta-interferons are widely prescribed platform therapies for patients with multiple sclerosis (MS). We accessed a cohort of patients with relapsing-onset MS from British Columbia, Canada (1995–2013), to examine the potential survival advantage associated with beta-interferon exposure using a marginal structural model. Accounting for potential treatment-confounder feedback between comorbidity, MS disease progression, and beta-interferon exposure, we found an association between beta-interferon exposure of at least 6 contiguous months and improved survival (hazard ratio (HR) = 0.63, 95% confidence interval 0.47, 0.86). We also assessed potential effect modifications by sex, baseline age, or baseline disease duration, and found these factors to be important effect modifiers. Sparse follow-up due to variability in patient contact with the health system is one of the biggest challenges in longitudinal analyses. We considered several single-level and multilevel multiple imputation approaches to deal with sparse follow-up and disease progression information; both types of approach produced similar estimates. Compared to ad hoc imputation approaches, such as linear interpolation (HR = 0.63), and last observation carried forward (HR = 0.65), all multiple imputation approaches produced a smaller hazard ratio (HR = 0.53), although the direction of effect and conclusions drawn concerning the survival advantage remained the same.

Whether ACE (angiotensin-converting enzyme) inhibitors and angiotensin receptor blockers modify colorectal cancer risk remains controversial. We aimed to determine association between their use and colorectal cancer risk after a negative baseline colonoscopy. This is a territory-wide retrospective cohort study recruiting patients aged ≥40 who had undergone colonoscopy between 2005 and 2013. Exclusion criteria included colorectal cancer detected 3years (adjusted hazard ratio, 1.18 [95% CI, 0.88–1.57]); every single year increase in the drug use was associated with 5% reduction in adjusted hazard ratio risk. ACE inhibitors/angiotensin receptor blocker were associated with a lower colorectal cancer risk in a duration-response manner.

Various psychological and biological pathways have been proposed as mediators between childhood adversity (CA) and psychosis. A systematic review of the evidence in this domain is needed. Our aim is to systematically review the evidence on psychological and biological mediators between CA and psychosis across the psychosis spectrum. This review followed PRISMA guidelines. Articles published between 1979 and July 2019 were identified through a literature search in OVID (PsychINFO, Medline and Embase) and Cochrane Libraries. The evidence by each analysis and each study is presented by group of mediator categories found. The percentage of total effect mediated was calculated. Forty-eight studies were included, 21 in clinical samples and 27 in the general population (GP) with a total of 82 352 subjects from GP and 3189 from clinical studies. The quality of studies was judged as ‘fair’. Our results showed (i) solid evidence of mediation between CA and psychosis by negative cognitive schemas about the self, the world and others (NS); by dissociation and other post-traumatic stress disorder symptoms; and through an affective pathway in GP but not in subjects with disorder; (iii) lack of studies exploring biological mediators. We found evidence suggesting that various overlapping and not competing pathways involving post-traumatic and mood symptoms, as well as negative cognitions contribute partially to the link between CA and psychosis. Experiences of CA, along with relevant mediators should be routinely assessed in patients with psychosis. Evidence testing efficacy of interventions targeting such mediators through cognitive behavioural approaches and/or pharmacological means is needed in future.

Although the association between stress and poor reproductive health is well established, this association has not been examined from a life course perspective. Using data from the National Longitudinal Survey of Youth 1997 cohort (N = 1652), we fit logistic regression models to test the association between stressful life events (SLEs) (e.g., death of a close relative, victim of a violent crime) during childhood, adolescence, and early adulthood and later experiences of infertility (inability to achieve pregnancy after 12 months of intercourse without contraception) reported by female respondents. Because reactions to SLEs may be moderated by different family life experiences, we stratified responses by maternal responsiveness (based on the Conger and Elder Parent-Youth Relationship scale) in adolescence. After adjusting for demographic and environmental factors, in comparison to respondents with one or zero SLEs, those with 3 SLEs and ≥ 4 SLEs had 1.68 (1.16, 2.42) and 1.88 (1.38, 2.57) times higher odds of infertility, respectively. Respondents with low maternal responsiveness had higher odds of infertility that increased in a dose–response manner. Among respondents with high maternal responsiveness, only those experiencing four or more SLEs had an elevated risk of infertility (aOR = 1.53; 1.05, 2.25). In this novel investigation, we demonstrate a temporal association between the experience of SLEs and self-reported infertility. This association varies by maternal responsiveness in adolescence, highlighting the importance of maternal behavior toward children in mitigating harms associated with stress over the life course.

Background The ABCG2 rs2231142 single nucleotide polymorphism (SNP) is one of the most significant genetic variants associated with hyperuricemia (HUA) in Asian populations. However, the risk of ABCG2 rs2231142 variants for HUA could interact with other important HUA risk variants and cardiovascular factors. This study investigated the effects of the combined association among ABCG2 rs2231142 and multiple HUA genetic variants or cardiovascular risk factors on HUA risk and serum uric acid (sUA) levels in an elderly Chinese population. Methods A total of 1206 participants over 65 years old were enrolled in this study. Physical and laboratory examinations were performed for all participants. The ABCG2 rs2231142, SLC2A9 rs3733591, and SLC22A12 rs893006 SNPs were assayed using a standardized protocol. Logistic regression analysis and liner regression were adjusted respectively to account for the association between ABCG2 rs2231142 and other genetic variants, as well as between cardiovascular risk factors and HUA risk and sUA levels. Results The prevalence of HUA was 14.71% in the elderly community-dwelling population. The ABCG2 rs2231142 risk T allele was associated with HUA risk (odds ratio (OR) = 1.63, 95% confidence interval (CI): 1.27–2.11; p = 1.65 × 10− 4) and with increased sUA levels (Beta = 0.16, p = 6.75 × 10− 9) in the whole study population. Linear regression analysis showed that the mean sUA level increased linearly with the number of risk alleles of the three candidate genetic variants (Beta = 0.18, p = 1.94 × 10− 12) The joint effect of the ABCG2 rs2231142 T allele and cardiovascular risk factors (obesity, hypertension and dyslipidemia) was also associated with increased HUA risk and sUA levels. Each copy of the risk T allele was significantly associated with enhanced HUA risk in patients with hypertriglyceridemia (OR = 2.52, 95% CI: 1.33–4.60; p = 0.003) compared to controls. Conclusion Our findings reinforce the importance of the ABCG2 rs2231143 variant as a crucial genetic locus for HUA in Chinese populations and demonstrated the combined effects of multiple genetic risk variants and cardiovascular risk exposures on HUA risk and increased sUA level.

ObjectivesGroup-based pain management programs (GPMPs) have been found to significantly improve quality of life and other pain outcome measures in patients with chronic musculoskeletal pain. The aims of this meta-analysis were to reevaluate the overall effect of GPMPs on various pain outcomes for individuals experiencing chronic musculoskeletal conditions and to explore moderator variables that potentially contribute to the overall efficacy of GPMPs.MethodsUsing the R package called metaphor and RevMan, we estimated the overall effectiveness of GPMPs on various pain outcome measures. The differential effectiveness of GPMPs was examined by conducting a mixed-effects meta-analytic model using various study-level characteristics. Moderator analyses included three content moderator variables and seven format moderator variables. Receiver operating characteristic curves investigated optimal points in some of the moderator variable analysis results.ResultsSignificant overall main effects of GPMPs were found on all the explored outcome measures in this study (P Discussion and Clinical RelevanceGPMPs have a statistically significant overall effect on all explored pain outcome measures. The investigation into content and structural moderators suggests that certain GPMP design factors have a greater effect on pain outcomes than do content factors. Therefore, GPMP structural designs appear to be important in reducing pain and improving quality of life for patients with chronic pain and warrant further investigation.

Objective\ud To better characterize differences in interictal sensory experience in adults with migraine and more comprehensively describe the relevance of anxiety to these experiences.\ud \ud Background\ud Evidence suggests that sensitivity to sensory input may not be limited to migraine attacks but continues between them. However, there is a need to better understand whether this is the case across senses, and to clearly distinguish sensory experience from measured sensory threshold, which are not straightforwardly related. Previous literature also indicates a co-occurrence between sensory sensitivity, migraine, and anxiety, but this relationship remains to be fully elucidated.\ud \ud Methods\ud The present cross-sectional study used online questionnaires to investigate how self-reported sensory experiences relate to migraine in a large community sample including 117 individuals with probable migraine and 827 without. Mediation analyses were also used to determine whether any relationship between migraine and sensory sensitivity was mediated by anxiety.\ud \ud Results\ud Significant increases in subjective reports of sensory sensitivity (d = 0.80) and sensory avoidance (d = 0.71) were found in participants with migraine. Anxiety symptoms partially mediated the relationship between subjective sensory sensitivity and migraine. Finally, visual, movement, and auditory subscales were found to provide unique explanatory variance in analyses predicting the incidence of migraine (area under the curve = 0.73, 0.69, 0.62 respectively).\ud \ud Conclusion\ud Subjective sensory sensitivities are present between attacks and across senses in individuals with migraine. Anxiety symptoms are relevant to this relationship; however, sensory sensitivities appear to exist independent of this affective influence. The implications of interictal sensitivities for the daily lives of those with migraine should, therefore, be considered in clinical management wherever appropriate.

Background Given the important repercussions that sociodemographic factors can have on physical activity, especially in the field of leisure, and cardiometabolic risk, it seems relevant to analyze the implications of these variables on the relationship between physical activity in leisure time (LTPA) and cardiometabolic risk. In this sense, the present study aims to verify the moderating role of biologic and socioeconomic factors in the relationship between LTPA and cardiometabolic risk in adolescents in southern Brazil. Methods Cross-sectional study that included 1596 adolescents selected at random (58.2% girls), aged between 10 and 17 years. LTPA, biological and socioeconomic factors were assessed using a self-reported questionnaire and the cardiometabolic risk score (total cholesterol/HDL-c ratio, triglycerides, fasting glucose, systolic blood pressure, and waist circumference, considering the participant’s age and sex) was included as an outcome. Associations and moderations were tested by multiple linear regression models. Results It was observed a positive interaction of LTPA and sex (p = 0.048) and LTPA and school system (p = 0.037), and negative interaction of LTPA and skin color (p = 0.040), indicating that these factors were moderators in the relationship between LTPA and clustered cardiometabolic risk score (cMetS) in adolescents. A reduction in cardiometabolic risk was observed according to the increase in weekly minutes of LTPA among boys, non-white adolescents, and students from municipal schools. Conclusions The association between LTPA and cardiometabolic risk was moderated by sex, skin color, and school system in adolescents from southern Brazil.

In medicine, the positive Hawthorne effect is defined as decreased symptom expression due to being observed. This effect occurs in addition to the decrease in symptom experience due to the placebo effect. Symptom overexpression, in contrast, whether related to conscious or to unconscious factors, defines the negative Hawthorne effect, which should be distinguished from the nocebo effect, defined as an increase in symptom experience. For instance, the negative Hawthorne effect can result in patients who seem fully relaxed evaluating their pain intensity at 11 on a 10-point Scale. The negative Hawthorne effect stems from multiple factors including a wish to receive greater consideration or priority management status; concern about failing to meet criteria for receiving a new treatment or being included in a therapeutic trial; conformism related to cultural factors or to circumstance (e.g., avoiding the canceling of a surgical procedure in the event of a last-minute improvement); disease mongering; a desire to be taken seriously by family and friends; a quest for secondary benefits; use of the evaluation to express frustration about being ill or bitterness at receiving a lower level of support; a gap between the expectation of complete relief and the true effectiveness of treatments; and pain exacerbation, with loss of reliability of pain intensity measurements, due to anxiety, guilt, depression, nervosity, catastrophizing, kinesiophobia, or repeated evaluations using methods that involve negative suggestions such as considering the worst pain imaginable. A sequence of a strong negative Hawthorne effect before treatment prescription followed by a strong positive Hawthorne effect after treatment initiation may make a greater contribution than the placebo effect to the improvements produced by treatments for pain.

Background Growing evidence shows that clinical and molecular subtypes of prostate cancer (PCa) have specific risk factors. Observational studies suggest that physical activity may lower the risk of aggressive PCa. To our knowledge, the association between physical activity and PCa defined by TMPRSS2:ERG has not been evaluated. Objective To prospectively examine the association between physical activity and risk of PCa defined by clinical features and TMPRSS2:ERG. Design, setting, and participants We studied 49 160 men aged 40–75 yr in the Health Professionals Follow-up Study from 1986 to 2012. Data was collected at baseline and every 2 yr with >90% follow-up. Total and vigorous physical activity were measured in metabolic equivalent of task (MET)-h/wk. Outcome measures and statistical analysis Advanced PCa was defined as stage T3b, T4, N1, or M1 at diagnosis and lethal PCa as distant metastases or death due to disease over follow-up. Presence of TMPRSS2:ERG was estimated by immunohistochemistry of ERG protein expression. Cox proportional hazards models were used to obtain multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for incidence of subtype-specific PCa. Results and limitations During 26 yr of follow-up, 6411 developed PCa overall and 888 developed lethal disease. There were no significant associations between total physical activity and risk of PCa in the overall cohort. In multivariable-adjusted models, men in the highest quintile of vigorous activity had a significant 30% lower risk of advanced PCa (HR: 0.70, 95% CI: 0.53–0.92) and 25% lower risk of lethal PCa (HR: 0.75, 95% CI: 0.59–0.94) than men in the lowest quintile of vigorous activity. The association was independent of screening history. Vigorous activity was not associated with total PCa in the overall cohort but was inversely associated among highly screened men (top vs bottom quintile, HR: 0.83, 95% CI: 0.70–0.97). Of all cases, 945 were assayed for ERG (48% ERG-positive). Men with higher vigorous activity had a lower risk of ERG-positive PCa (top vs bottom quintile, HR: 0.71, 95% CI: 0.52–0.97). There was no significant association with the risk of ERG-negative disease (p heterogeneity = 0.09). Conclusions Our study confirms that vigorous physical activity is associated with lower risk of advanced and lethal PCa and provides novel evidence for a lower risk of TMPRSS2:ERG-positive disease. Patient summary The identification of modifiable lifestyle factors for prevention of clinically important prostate cancer (PCa) is needed. In this report, we compared risk of PCa in men with different levels of physical activity. Men with higher vigorous activity had a lower risk of developing advanced and lethal PCa and PCa with the common TMPRSS2:ERG gene fusion.

Objectives Observational cohort studies in early RA are a key source of evidence, despite inconsistencies in methodological approaches. This narrative review assesses the spectrum of methodologies used in addressing centre-level effect and case-mix adjustment in early RA observational cohort studies. Methods An electronic search was undertaken to identify observational prospective cohorts of >100 patients recruited from two or more centres, within 2 years of an RA or early inflammatory arthritis diagnosis. References and author publication lists of all studies from eligible cohorts were assessed for additional cohorts. Results Thirty-four unique cohorts were identified from 204 studies. Seven percent of studies considered centre in their analyses, most commonly as a fixed effect in regression modelling. Reporting of case-mix variables in analyses varied widely. The number of variables considered in case-mix adjustment was higher following publication of the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement in 2007. Conclusion Centre effect is unreported or inadequately accounted for in the majority of RA observational cohorts, potentially leading to spurious inferences and obstructing comparisons between studies. Inadequate case-mix adjustment precludes meaningful comparisons between centres. Appropriate methodology to account for centre and case-mix adjustment should be considered at the outset of analyses.

Objective: This study aimed to investigate whether the association between a validated genetic profile risk score for BMI (GPRS‐BMI) (based on 93 single‐nucleotide polymorphisms) and phenotypic obesity (BMI) was modified by the combined categories of physical activity (PA) and sedentary behaviors in a large population‐based study. Methods: This study included cross‐sectional baseline data from 338,216 white European adult men and women aged 37 to 73 years. Interaction effects of GPRS‐BMI with the combined categories of PA and sedentary behaviors on BMI were investigated. Results: There was a significant interaction between GPRS‐BMI and the combined categories of objectively measured PA and total sedentary behavior (P[interaction] = 3.5 × 10−6); among physically inactive and highly sedentary individuals, BMI was higher by 0.60 kg/m2 per 1‐SD increase in GPRS‐obesity (P = 8.9 × 10−50), whereas the relevant BMI difference was 38% lower among physically active individuals and those with low sedentary time (β: 0.37 kg/m2; P = 2.3 × 10−51). A similar pattern was observed for the combined categories of objective PA and TV viewing (inactive/high TV viewing β: 0.60 vs. active/low TV viewing β: 0.40 kg/m2; P[interaction] = 2.9 × 10−6). Conclusions: This study provides evidence that combined categories of PA and sedentary behaviors modify the extent to which genetic predisposition to obesity results in higher BMI.

Although young onset dementia (YOD) causes high levels of burden and distress, factors that contribute to its onset are not well understood. Identifying relevant modifiable risk and protective factors for YOD can inform efforts to prevent or delay onset of symptoms to later in life.Studies of modifiable factors for YOD have increased in frequency in recent years. Poor educational attainment and low socioeconomic status, a history of heavy alcohol use, and poor cardiovascular health may be key targets for YOD prevention or delay. Traumatic brain injury has attracted significant attention but evidence of its importance is limited except in cases occurring secondarily to the injury.A growing body of evidence suggests that modifiable risk factors have a role in modulating the age of dementia onset. Clinicians should be aware that many people with YOD will present with complex histories of multifactorial (including modifiable and nonmodifiable) risk exposure. Exploring trajectories of risk and gene-environment interactions is an important future research direction and will inform targeted prevention efforts.

Objectives This study examined the longitudinal relationships between subjective age (SA) and future functional status in later life, via depressive symptoms. Additionally, we assessed the role of subjective nearness to death (SNtD) as a potential moderator within these pathways. Methods Older adults (average age 81.14 years at T1) were interviewed once a year for 3 consecutive years (N = 224 at T1, N = 178 at T2, and N = 164 at T3). Participants reported their SA, SNtD, depressive symptoms, and functional status. Additionally, grip strength was employed as an objective measure of functional status. Results Data analysis revealed distinct pathways leading from T1 SA to T3 functional status through T2 depressive symptoms. Moreover, T1 SNtD was found to significantly moderate most of these indirect pathways, so that the mediation model of T1 SA–T2 depressive symptoms–T3 functional status was mostly significant among those who felt closer to death. Discussion The findings contribute to our understanding of the underlying mechanism through which SA predicts long-term functioning sequelae by underscoring the indirect effect of depressive symptoms. They further indicate the importance of gauging the effects of SNtD on these longitudinal relationships. Present results may further contribute to establishing an integrative model for predicting long-term functional outcomes based on older adults’ earlier subjective views of aging.

The Halo Effect is a widely studied phenomenon that interests multiple disciplines. The relationship between Aesthetics Appearance and perceived Trustworthiness has especially gathered the attention of social scientists. While experimental works compared the strength of the Halo Effect in different situations (e.g. different genders’ faces), little is known about the stability of the Halo. During the COVID-19 pandemic, we have been urged to distance ourselves from others. Similar suggestions may alter the relationship between Aesthetic Appearance and Perceived Trustworthiness. Moreover, previous works reported that individuals’ attachment styles affected their emotional responses to the pandemic. Individuals’ attachment styles may influence the magnitude of change of the Halo. Here we investigate how priming (Social Distancing or Contact with others) affects the strength of the Halo Effect, with respect to individuals’ attachment styles. Participants (N = 298) rated the Aesthetics and Perceived Trustworthiness of strangers’ faces (N = 96) presented twice, before and after the presentation of a prime. Results revealed that individuals’ attachment styles affect the strength of the Halo. However, we found no evidence supporting the fact that different attachment styles lead to differences in the magnitude of changes after priming. Results help shed light on how attachment styles influence individuals’ impression formation. Ministry of Education (MOE) Published version This research was supported by grants from the NAP SUG to GE (M4081597, 2015-2021). Ministry of Education, Singapore, under its Academic Research Fund Tier 1 (RT10/19 and RG55/18). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Background: Treatment with sacubitril-valsartan reduces mortality and heart failure (HF) events in HF with reduced ejection fraction and may reduce HF hospitalization in women with HF with preserved ejection fraction. Methods: EVALUATE-HF randomized 464 participants (109 women) with HF with reduced ejection fraction to sacubitril-valsartan or enalapril for 12 weeks. Documented left ventricular ejection fraction (LVEF) ≤0.40 within the prior 12 months was required, although core laboratory LVEF>0.40 was permitted. Assessments of aortic stiffness (pulse pressure and characteristic impedance, Z c ) were performed at baseline and at trough and 4 hours postdose at weeks 4 and 12. Results: In models of change from baseline adjusted for baseline value, treatment with sacubitril-valsartan produced greater overall reductions in mean arterial pressure (treatment group difference, −3.0±0.8 mm Hg, P P c were greater in the sacubitril-valsartan group (−16±6 dyne×second/cm 5 , P =0.012). Post hoc analyses found evidence of effect modification by LVEF (interaction P =0.036). With LVEFc were greater in the sacubitril-valsartan group (trough, −3±8 dyne×second/cm 5 versus post-dose, −17±8 dyne×second/cm 5 ; interaction P =0.024) with no sex difference (treatment×sex interaction, P =0.3). With LVEF≥0.40, treatment with sacubitril-valsartan was associated with greater overall reductions in Z c in women (women, −80±21 dyne×second/cm 5 versus men, −20±13 dyne×second/cm 5 ; interaction P =0.019). Conclusions: In prespecified analyses that include pre- and postdose assessments at 4 and 12 weeks, treatment with sacubitril-valsartan was associated with greater postdose reductions in aortic Z c . In a post hoc analysis, sacubitril-valsartan was associated with sustained reductions in Z c in women with LVEF≥0.40. Registration: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT02874794.

Background Proteomic biomarkers related to cardiovascular disease risk factors may offer insights into the pathogenesis of cardiovascular disease. We investigated whether modifiable lifestyle risk factors for cardiovascular disease are associated with distinctive proteomic signatures. Methods and Results We analyzed 1305 circulating plasma proteomic biomarkers (assayed using the SomaLogic platform) in 897 FHS (Framingham Heart Study) Generation 3 participants (mean age 46±8 years; 56% women; discovery sample) and 1121 FOS (Framingham Offspring Study) participants (mean age 52 years; 54% women; validation sample). Participants were free of hypertension, diabetes mellitus, and clinical cardiovascular disease. We used linear mixed effects models (adjusting for age, sex, body mass index, and family structure) to relate levels of each inverse‐log transformed protein to 3 lifestyle factors (ie, smoking, alcohol consumption, and physical activity). A Bonferroni‐adjusted P value indicated statistical significance (based on number of proteins and traits tested, P −6 in the discovery sample; P −4 in the validation sample). We observed statistically significant associations of 60 proteins with smoking (37/40 top proteins validated in FOS), 30 proteins with alcohol consumption (23/30 proteins validated), and 5 proteins with physical activity (2/3 proteins associated with the physical activity index validated). We assessed the associations of protein concentrations with previously identified genetic variants (protein quantitative trait loci) linked to lifestyle‐related disease traits in the genome‐wide‐association study catalogue. The protein quantitative trait loci were associated with coronary artery disease, inflammation, and age‐related mortality. Conclusions Our cross‐sectional study from a community‐based sample elucidated distinctive sets of proteins associated with 3 key lifestyle factors.

Author(s): Wessells, K Ryan; Arnold, Charles D; Stewart, Christine P; Prado, Elizabeth L; Abbeddou, Souheila; Adu-Afarwuah, Seth; Arnold, Benjamin F; Ashorn, Per; Ashorn, Ulla; Becquey, Elodie; Brown, Kenneth H; Byrd, Kendra A; Campbell, Rebecca K; Christian, Parul; Fernald, Lia CH; Fan, Yue-Mei; Galasso, Emanuela; Hess, Sonja Y; Huybregts, Lieven; Jorgensen, Josh M; Kiprotich, Marion; Kortekangas, Emma; Lartey, Anna; Le Port, Agnes; Leroy, Jef L; Lin, Audrie; Maleta, Kenneth; Matias, Susana L; Mbuya, Mduduzi NN; Mridha, Malay K; Mutasa, Kuda; Naser, Abu Mohd; Paul, Rina R; Okronipa, Harriet; Ouedraogo, Jean-Bosco; Pickering, Amy J; Rahman, Mahbubur; Schulze, Kerry; Smith, Laura E; Weber, Ann M; Zongrone, Amanda; Dewey, Kathryn G | Abstract: ABSTRACTBackgroundSmall-quantity lipid-based nutrient supplements (SQ-LNS) have been shown to reduce the prevalence of anemia and iron deficiency among infants and young children, but effects on other micronutrients are less well known. Identifying subgroups who may experience greater benefits from SQ-LNS, or who are more likely to respond to the intervention, may facilitate the development of public health policies and programs.ObjectiveOur objective was to identify study-level and individual-level modifiers of the effect of SQ-LNS on child hematological and micronutrient status outcomes.MethodsWe conducted a two-stage meta-analysis of individual participant data from 13 randomized controlled trials of SQ-LNS provided to children 6 to 24 months of age in low- and middle-income countries (n = 15,946). Outcomes were hemoglobin (Hb), inflammation-adjusted plasma ferritin, soluble transferrin receptor, zinc, retinol and retinol binding protein (RBP), and erythrocyte zinc protoporphyrin, and respective dichotomous outcomes indicative of anemia and micronutrient deficiency. We generated study-specific estimates of SQ-LNS vs. control, including main effects and subgroup estimates for individual-level effect modifiers, and pooled the estimates using fixed-effects models. We used random effects meta-regression to examine potential study-level effect modifiers.ResultsProvision of SQ-LNS decreased the prevalence of anemia (Hb l 110 g/L) by 16% (relative reduction), iron deficiency (plasma ferritin l 12 µg/L) by 56% and iron deficiency anemia (IDA; Hb l 110 g/L and plasma ferritin l 12 µg/L) by 64%. We observed positive effects of SQ-LNS on hematological and iron status outcomes within all subgroups of the study-level and individual-level effect modifiers, but effects were larger in certain subgroups. For example, effects of SQ-LNS on anemia and iron status were greater in trials that provided SQ-LNS for g 12 months and provided 9 mg/d vs. l 9 mg iron/d, and among later-born (vs. first-born) children. There was no effect of SQ-LNS on plasma zinc or retinol, but there was a 7% increase in plasma RBP and a 56% reduction in vitamin A deficiency (RBP l 0.70 µmol/L), with little evidence of effect modification by individual-level characteristics.ConclusionsSQ-LNS provided to infants and young children 6-24 months of age can substantially reduce the prevalence of anemia, iron deficiency, and IDA across a range of individual, population and study design characteristics. Policy-makers and program planners should consider SQ-LNS within intervention packages to prevent anemia and iron deficiency. This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42020156663.

Background: Heart failure (HF) is a heterogeneous disease characterized by significant metabolic disturbances; however, the breadth of metabolic dysfunction before the onset of overt disease is not well understood. The purpose of this study was to determine the association of circulating metabolites with incident HF to uncover novel metabolic pathways to disease. Methods: We performed targeted plasma metabolomic profiling in a deeply phenotyped group of Black adults from the JHS (Jackson Heart Study; n=2199). We related metabolites associated with incident HF to established etiological mechanisms, including increased left ventricular mass index and incident coronary heart disease. Furthermore, we evaluated differential associations of metabolites with HF with preserved ejection fraction versus HF with reduced ejection fraction. Results: Metabolites associated with incident HF included products of posttranscriptional modifications of RNA, as well as polyamine and nitric oxide metabolism. A subset of metabolite-HF associations was independent of well-established HF pathways such as increased left ventricular mass index and incident coronary heart disease and included homoarginine (per 1 SD increase in metabolite level, hazard ratio, 0.77; P =1.2×10 −3 ), diacetylspermine (hazard ratio, 1.34; P =3.4×10 −3 ), and uridine (hazard ratio, 0.79; P , 3×10 −4 ). Furthermore, metabolites involved in pyrimidine metabolism (orotic acid) and collagen turnover ( N -methylproline) among others were part of a distinct metabolic signature that differentiated individuals with HF with preserved ejection fraction versus HF with reduced ejection fraction. Conclusions: The integration of clinical phenotyping with plasma metabolomic profiling uncovered novel metabolic processes in nontraditional disease pathways underlying the heterogeneity of HF development in Black adults.

Key Points Question What are modifiable preoperative factors associated with developing chronic pain after distal radius fracture surgery? Findings In this secondary analysis of a randomized clinical trial with 146 participants, each 10-point increase in preoperative pain score was associated with 17% increased odds of chronic pain, and a 1-week delay in surgical intervention was associated with more than triple the odds of experiencing chronic pain. Internal fixation was associated with decreased risk of chronic pain compared with external fixation or pinning. Meaning In this study, earlier time to surgery, adequate preoperative pain control, and internal fixation were associated with lower risk of chronic pain development among patients with distal radius fracture who were treated surgically., This secondary analysis identifies modifiable preoperative factors that are significantly associated with developing chronic pain among patients with distal radius fractures who are treated surgically., Importance Despite appropriate treatment, many patients who sustain distal radius fractures (DRFs) report persistent wrist pain. Chronic musculoskeletal pain is among the leading health problems in the elderly population associated with significant personal and societal burden. Objective To identify modifiable preoperative factors that are significantly associated with developing chronic pain. Design, Setting, and Participants This is a secondary analysis of the Wrist and Radius Injury Surgical Trial (WRIST), a randomized multicenter clinical trial of 24 study sites in the United States, Canada, and Singapore that enrolled patients from April 10, 2012, to December 31, 2016. Adults older than 60 years who sustained closed extra-articular DRFs, were treated operatively, and completed 12-month Michigan Hand Outcomes Questionnaires (MHQs) were included in this study. Analysis was conducted from September to December 2019. Interventions Volar locking plate internal fixation, external fixation, or percutaneous pinning. Main Outcomes and Measures 12-month MHQ pain domain score. Inverse probability weighted logistic regression was used to identify factors associated with of chronic pain. Results A total of 146 patients with DRF who were treated operatively and had 12-month MHQ scores met inclusion criteria. The mean (SD) patient age was 68.9 (7.2) years, 128 (87.6%) were women, and 93 (63.7%) were retired. Chronic pain was present in 87 patients (59.6%) and absent in 59 patients (40.4%) at 1-year follow-up. A 1-week delay in surgery was associated with more than triple the odds of developing chronic pain (odds ratio [OR], 3.65; 95% CI, 1.48-9.00), and each 10-point increase in preoperative pain was associated with a 17% increase in the odds of experiencing chronic pain (OR, 1.17; 95% CI, 1.02-1.34). Internal fixation was associated with decreased odds of developing chronic pain compared with the other 2 procedures (OR, 0.29; 95% CI, 0.10-0.90). Conclusions and Relevance In this study, preoperative pain, time to surgery, and procedure type were modifiable factors associated with chronic pain 1 year after DRF treated with surgery. Adequate pain control in patients with acute DRFs even before definitive surgical management and earlier fixation for patients requiring surgery may decrease the risk of developing chronic pain. Internal fixation may decrease the risk of chronic pain after DRF surgery, compared with percutaneous pinning or external fixation. Trial Registration ClinicalTrials.gov Identifier: NCT01589692

Background/Purpose Most studies examining the components of the fear-avoidance model have examined processes at the group level. The current study used ecological momentary assessments to: (a) investigate the group and intraindividual relationships between pain fear, avoidance, and pain severity, (b) identify any heterogeneity between these relationships, and (c) explore the role of moderators to explain such heterogeneity. Methods Seventy-one pediatric patients with chronic abdominal pain (M = 13.34 years, standard deviation = 2.67 years) reported pain fear, avoidance, and pain severity four times per day over 14 days. Results Results indicated significant individual differences in the relationship between pain fear and pain avoidance predicting pain severity. Child age helped explain the heterogeneity in the relationships between pain avoidance and pain severity such that older children had a stronger and more positive relationship between these variables. The random effect between pain fear and pain severity also indicated a moderator trend of child age such that older children were likely to have a stronger and more positive relationship. Conclusions The present study extends the fear-avoidance model by highlighting the importance of identifying potential individual differences when examining pain fear, avoidance, and pain severity. Furthermore, the current study suggests that child development should be considered in the model. However, future randomized control designs are necessary to explore the causal relationships between pain fear and avoidance on pain severity and potential developmental differences.

Background The Hawthorne Effect is the change in behaviour by subjects due to their awareness of being observed and is evident in both research and clinical settings as a result of various forms of observation. When the Hawthorne effect exists, it is short-lived, and likely leads to increased productivity, compliance, or adherence to standard protocols. This study is a qualitative component of an ongoing multicentre study, examining the role of Incisional Negative Pressure Wound Therapy after vascular surgery (INVIPS Trial). Here we examine the factors that influence hygiene and the role of the Hawthorne effect on the adherence of healthcare professionals to standard hygiene precautions. Methods This is a qualitative interview study, investigating how healthcare professionals perceive the observation regarding hygiene routines and their compliance with them. Seven semi-structured focus group interviews were conducted, each interview included a different staff category and one individual interview with a nurse from the Department for Communicable Disease Control. Additionally, a structured questionnaire interview was performed with environmental services staff. The results were analysed based on the inductive qualitative content analysis approach. Results The analysis revealed four themes and 12 subthemes. Communication and hindering hierarchy were found to be crucial. Healthcare professionals sought more personal and direct feedback. All participants believed that there were routines that should be adhered to but did not know where to find information on them. Staff in the operating theatre were most meticulous in adhering to standard hygiene precautions. The need to give observers a clear mandate and support their work was identified. The staff had different opinions concerning the patient’s awareness of the importance of hygiene following surgery. The INVIPS Trial had mediated the Hawthorne effect. Conclusion The results of this study indicate that the themes identified, encompassing communication, behaviour, rules and routines, and work environment, influence the adherence of healthcare professionals to standard precautions to a considerable extent of which many factors could be mediated by a Hawthorne effect. It is important that managers within the healthcare system put into place an improved and sustainable hygiene care to reduce the rate of surgical site infections after vascular surgery.

Despite evidence linking obesity with increased mortality, older adults with excessive adiposity seem protected, resulting in a so-called obesity paradox. Obesity is characterized by leptin resistance, which contributes to increased risk of all-cause mortality. Therefore, lifestyle factors, such as physical fitness, that lower leptin independent of adiposity may be confounding the obesity paradox. To investigate this, we evaluated whether physical fitness moderated the relationship between leptin and adiposity. We found older adults with higher fitness had lower body mass (r(39) = -0.43, p < 0.01), leptin (r(39) = -0.29, p = 0.03) and inflammation (IL-1β: (r(39) = -0.69, p < 0.01); TNF-α: (r(39) = -0.30, p = 0.03)). Fitness moderated the relationship between leptin and adiposity (F(5, 37) = 3.73, p < 0.01, R2 = 0.33) to reveal the obesity paradox in moderately and high fit individuals (b = 216.24, t(37) = 1.46, p = 0.15; b= -88.10, t(37) = -0.49, p = 0.63) but not in low fit individuals. These results show the link between obesity and mortality may not be dependent on total adiposity, but rather on endocrine function and adipocyte leptin secretion. These results have important implications for older adults struggling to maintain healthy body composition and suggest that fitness may promote overall wellbeing.

OBJECTIVES This meta-analysis aimed to assess the overall effect of therapeutic pain neuroscience education (TPNE) on chronic musculoskeletal pain and to further assess whether such an effect differs by TPNE dosage as well as other treatment format components. Dosage included the number of TPNE sessions provided as well as the amount of time per TPNE session. Structural components included TPNE provided alone as treatment or combined with other pain management modalities, as well as the inclusion of group-based treatment sessions. METHODS Electronic databases were utilized to search for randomized controlled trials that included TPNE. The overall effectiveness of TPNE was estimated on 4 pain outcome measures, including kinesiophobia, pain intensity, pain disability, and pain catastrophizing. The differential effectiveness of TPNE was examined using a mixed-methods moderator analysis on various study-level characteristics to identify potential moderators affecting the overall results. RESULTS Significant effects of TPNE were found on all the outcome measures. The only moderator that displayed a significant effect was group-based treatment on kinesiophobia (z = -2.23, P

Background Home visits by paraprofessional community health workers (CHWs) has been shown to improve maternal and child health outcomes in research studies in many countries. Yet, when these are scaled or replicated, efficacy disappears. An effective CHW home visiting program in peri-urban Cape Town found maternal and child health benefits over the 5 years point but this study examines if these benefits occur in deeply rural communities. Methods A non-randomized, two-group comparison study evaluated the impact of CHW in the rural Eastern Cape from August 2014 to May 2017, with 1310 mother-infant pairs recruited in pregnancy and 89% were reassessed at 6 months post-birth. Results Home visiting had limited, but important effects on child health, maternal wellbeing and health behaviors. Mothers reported fewer depressive symptoms, attended more antenatal visits and had better baby-feeding practices. Intervention mothers were significantly more likely to exclusively breastfeed for 6 months (OR: 1.8; 95% CI: 1.1, 2.9), had lower odds of mixing formula with baby porridge (regarded as detrimental) (OR: 0.4; 95% CI: 0.2, 0.8) and were less likely to consult traditional healers. Mothers living with HIV were more adherent with co-trimoxazole prophylaxis (p Conclusion The impact of CHWs in a rural area was less pronounced than in peri-urban areas. CHWs are likely to need enhanced support and supervision in the challenging rural context.

The association between childhood adversity (CA) and psychosis has been extensively investigated in recent years. An increasing body of research has also focused on the mediating or moderating role of biological and psychological mechanisms, as well as other risk factors that might account for the link between CA and psychosis. We conducted a systematic search of the PsychINFO, Embase, Ovid, and Web of Science databases for original articles investigating the role of genetic vulnerabilities, environmental factors, psychological and psychopathological mechanisms in the association between CA and psychosis up to August 2019. We included studies with individuals at different stages of the psychosis continuum, from subclinical psychotic experiences to diagnosed disorders. From the 28 944 records identified, a total of 121 studies were included in this review. Only 26% of the studies identified met the criteria for methodological robustness. Overall, the current evidence suggests that CA may be associated with psychosis largely independently of genetic vulnerabilities. More consistent and robust evidence supports interaction between early and recent adversities, as well as the mediating role of attachment and mood symptoms, which is suggestive of an affective pathway between CA and psychosis across the continuum from subclinical experiences to diagnosable disorder. This review highlighted numerous methodological issues with the existing literature, including selection bias, heterogeneity of measurement instruments utilised, and lack of control for potential confounders. Future research should address these limitations to more accurately estimate mediation and moderation effects on the CA-psychosis association to inform the development of preventive interventions.

Background Common and rare variants, including those in the gene for the cardiac structural protein titin (TTN), have been implicated in the risk of developing atrial fibrillation (AF). However, the effect of genetic variants on risk of AF compared with established modifiable risk factors is unclear. The objective of this study was to evaluate the risk of AF and associated cardiovascular complications in TTN variant carriers and examine interactions between TTN variants or common variants and modifiable AF risk factors. Methods We used whole exome sequencing data of 49,881 individuals and genotyping data of 408,572 individuals from the UK Biobank to examine the associations of TTN variants, polygenic risk, and 4 risk factors (hypertension, diabetes, obesity, and smoking) with AF. Adjusted hazard ratios (aHRs) were calculated with the use of Cox proportional hazards models. Results TTN variant carrier status was associated with a higher risk of AF (aHR 2.10, 95% CI 1.59-2.79; P = 2.54 × 10−7) and higher risk of dilated cardiomyopathy in AF patients (aHR 10.39, 95% CI 5.31-20.33; P = 8.37 × 10−12). We identified additive effects between TTN variants and polygenic risk with hypertension, diabetes, obesity, and smoking on the risk of AF. Conclusions Genetic and modifiable cardiovascular risk factors contribute to the probability of developing AF. Our findings highlight the potential utility of incorporating data from targeted sequencing or genotyping of common variants to further inform AF risk stratification and aggressive management of modifiable cardiovascular risk factors.

Context Studies in mice and humans suggest that melanocortin-4 receptor (MC4R) deficiency affects body weight in a sex-/gender-dependent manner. However, similar evidence for type 2 diabetes (T2D) is scarce. Objective and Design We investigated whether sex/gender modifies the association between the loss-of-function MC4R p.Ile269Asn mutation and T2D in 6929 Mexican adults (3175 T2D cases and 3754 normal glucose tolerance [NGT] controls). The 2003 American Diabetes Association criteria were used to define NGT and T2D. The MC4R p.Ile269Asn mutation was genotyped in all participants using TaqMan technology. Results The MC4R p.Ile269Asn mutation was associated with T2D in 6929 Mexican adults (Ncontrols = 3754, Ncases = 3175, odds ratio [OR] = 2.00, 95% confidence interval [CI], 1.35-2.97; P = 5.7 × 10-4). The MC4R p.Ile269Asn mutation had a frequency of 0.86 and 1.05% in women with NGT and T2D, and 0.78 and 1.32% in men with NGT and T2D, respectively. We identified a significant interaction between the MC4R p.Ile269Asn mutation and sex/gender on T2D risk (P = 0.049). Although a strong association between the mutation and T2D was observed in men (Ncontrols = 2418, Ncases = 1807, OR = 2.63, 95% CI, 1.62-4.28, P = 9.3 × 10-5), results were not significant in women (Ncontrols = 1336, Ncases = 1368, OR = 1.16, 95% CI, 0.60-2.26, P = 0.65). Further adjustment for body mass index in the logistic regression model did not alter the sex-/gender-specific pattern of association (men: OR = 2.22, 95% CI, 1.34-3.67, P = 0.0019; women: OR = 1.02, 95% CI, 0.51-2.02, P = 0.95). Conclusion This is the first report of a male-specific association between the MC4R p.Ile269Asn loss-of-function mutation and T2D in the Mexican population.

Numerous studies demonstrate that the Hawthorne effect (behaviour change caused by awareness of being observed) increases health workers' hand hygiene adherence but it is not clear whether they are methodologically robust, what the magnitude of the effect is, how long it persists or whether it is the same across clinical settings. The objective of this review was to determine the rigour of the methods used to assess the Hawthorne effect on hand hygiene, effect size estimation, variations between clinical settings and persistence. To this end, a systematic literature review with meta-analysis was conducted. Nine studies met the criteria for the review. Methodological quality was variable. The Hawthorne effect ranged from -6.9% to 65.3%. It was 4.2% in one study conducted in intensive care and 16.4% in transplant units. It was most marked when data were collected across an entire hospital and in a group of general hospitals. Differences between wards in the same hospital were apparent. In the two studies where duration was estimated, the Hawthorne effect appeared transient. Despite methodological shortcomings, the review indicates clear evidence of a Hawthorne effect on general wards. There is evidence that it may vary between clinical speciality and across departments. The review identifies a need for standardized methodologies to measure the Hawthorne effect to overcome the dilemma of reporting the potentially inflated rates of adherence obtained through overt audit. Occasional covert audit could give a better estimation of true hand hygiene adherence but its acceptability and feasibility to health workers need to be explored.

Context The halo effect describes the improved surgical outcomes at trauma centers for nontrauma conditions. Objective To determine whether level 1 trauma centers have improved inpatient mortality for common but high-acuity nonsurgical diagnoses (eg, acute myocardial infarction [AMI], congestive heart failure [CHF], and pneumonia [PNA]) compared with non--level 1 trauma centers. Methods The authors conducted a population-based, retrospective cohort study analyzing data from the Healthcare Cost and Utilization Project State Inpatient Database and the American Hospital Association Annual Survey Database. Patients who were admitted with AMI, CHF, and PNA between 2006-2011 in Florida and California were included. Level 1 trauma centers were matched to non-level 1 trauma centers using propensity scoring. The primary outcome was risk-adjusted inpatient mortality for each diagnosis (AMI, CHF, or PNA). Results Of the 190,474 patients who were hospitalized for AMI, CHF, or PNA, 94,037 patients (49%) underwent treatment at level 1 trauma centers. The inpatient mortality rates at level 1 trauma centers vs non-level 1 trauma centers for patients with AMI was 8.10% vs 8.40%, respectively (P=.73); for patients with CHF, 2.26% vs 2.71% (P=.90); and for patients with PNA, 2.30% vs 2.70% (P=.25). Conclusion Level 1 trauma center designation was not associated with improved mortality for high-acuity, nonsurgical medical conditions in this study.

This cross-sectional study extracted data of 392 NHANES participants with elevated serum parathyroid hormone (PTH) concentrations from 2 cycles of the US National Health and Nutrition Examination Survey (NHANES) 2003–2006 and evaluated the association between serum (PTH) concentration and metabolic syndrome (MetS) to identify dietary and lifestyle factors that may modify that association. The primary outcome was MetS severity scores. Results of univariate linear regression analyses revealed that serum PTH concentrations correlated positively and significantly with MetS severity scores (β=0.399, p=0.030). After adjusting for gender, age, race, and alcohol consumption, results of multivariate analysis revealed that increased serum PTH concentration correlated significantly with higher MetS severity scores (β=0.413, p=0.045) in participants with moderate physical activity over the past 30 days. Serum PTH concentration also correlated significantly with higher MetS severity scores in participants with serum 25-hydroxyvitamin D deficiency (β=0.456 and p=0.014), those without vitamin D supplementation (β=0.524, p=0.028) and with higher protein intake (β=0.586 and p=0.030). In conclusion, increased serum PTH concentration is associated with higher MetS severity scores in participants with elevated serum PTH at baseline. The association between PTH concentration and MetS severity is moderated by participants’ physical activity levels, status of serum vitamin D, vitamin D supplementation, and daily protein intake.

OBJECTIVE To find prevalence of preterm birth in Pakistan and to explore its related risk factors. METHODS This analytical cross-sectional study was conducted from October 1, 2016, to September 30, 2017, at Hajvery University, Lahore, Pakistan, and data was collected from Obstetrics and Gynaecology departments of various hospitals in four provinces of the country. To find risk factors of preterm birth, data was divided into two groups: Group-1 consisted cases with preterm birth defined as gestational age

Purpose: Spontaneous eye-blink rate is the number of involuntary blinks performed during a certain period of time. Assessing blink rate in humans provides valuable physiological and behavioral data...

ObjectiveThis study examined the association of anxiety alone, depression alone and the presence of both anxiety and depression with preterm birth (PTB) and further examined whether neighbourhood socioeconomic status (SES) modified this association.DesignCohort study using individual-level data from two community-based prospective pregnancy cohort studies (All Our Families; AOF) and Alberta Pregnancy Outcomes and Nutrition (APrON) and neighbourhood SES data from the 2011 Canadian census.SettingCalgary, Alberta, Canada.ParticipantsOverall, 5538 pregnant women who were 15 years old were enrolled in the cohort studies between 2008 and 2012. 3341 women participated in the AOF study and 2187 women participated in the APrON study, with 231 women participated in both studies. Women who participated in both studies were only counted once.Primary and secondary outcome measuresPTB was defined as delivery prior to 37 weeks of gestation. Depression was defined as an Edinburgh Postnatal Depression Scale (EPDS) score of ≥13, anxiety was defined as an EPDS-anxiety subscale score of ≥6, and the presence of both anxiety and depression was defined as meeting both anxiety and depression definitions.ResultsOverall, 7.3% of women delivered preterm infants. The presence of both anxiety and depression, but neither of these conditions alone, was significantly associated with PTB (OR 1.6, 95% CI 1.1 to 2.3) and had significant interaction with neighbourhood deprivation (p=0.004). The predicted probability of PTB for women with both anxiety and depression was 10.0%, which increased to 15.7% if they lived in the most deprived neighbourhoods and decreased to 1.4% if they lived in the least deprived neighbourhoods.ConclusionsEffects of anxiety and depression on risk of PTB differ depending on where women live. This understanding may guide the identification of women at increased risk for PTB and allocation of resources for early identification and management of anxiety and depression.

BACKGROUND: Air pollution has been associated with various health outcomes. Its effect on hand-grip strength, a measurement of the construct of muscle strength and health status, remains largely unknown. METHODS: We used the survey data from 31,209 adults ≥ 50 years of age within Wave 1 of the Study on Global AGEing and Adult Health in six low- and middle-income countries. The outdoor concentration of fine particulate matter pollution (PM2.5) was estimated using satellite data. Domestic fuel type and ventilation were used as indicators of indoor air pollution. We used multilevel linear regression models to examine the association between indoor and outdoor air pollution and hand-grip strength, as well as the potential effect modifiers. RESULTS: We found inverse associations between both indoor and outdoor air pollution and hand-grip strength. Each 10 μg/m3 increase in 3 years' averaged concentrations of outdoor PM2.5 corresponded to 0.70 kg (95% CI: -1.26, -0.14) lower hand-grip strength; and compared with electricity/liquid/gas fuel users, those using solid fuels had lower hand-grip strength (β = -1.25, 95% CI: -1.74, -0.75). However, we did not observe a statistically significant association between ventilation and hand-grip strength. We further observed that urban residents and those having a higher education level had a higher association between ambient PM2.5 and hand-grip strength, and men, young participants, smokers, rural participants, and those with lower household income had higher associations between indoor air pollution and hand-grip strength. CONCLUSION: This study suggests that both indoor and outdoor air pollution might be important risk factors of poorer health and functional status as indicated by hand-grip strength.

BACKGROUND AND OBJECTIVES: Genome Wide Association Studies (GWAS) have identified genetic polymorphisms associated with bronchodilator response (BDR), but it is unknown how these associations change across life stages. We examined the impact of genetic variants on BDR from childhood to adulthood in asthmatics to uncover potential effect modification by age. METHODS: We searched the National Human Genome Research Institute (NHGRI) catalog of published GWAS to obtain a list of genetic associations with BDR, and tested them for effect modification by age in 604 subjects from the Childhood Asthma Management Program (CAMP), a clinical trial with longitudinal measures of BDR (age range 5 to 30 years). We performed longitudinal analyses using linear mixed models and visualized longitudinal changes in BDR using generalized additive models with repeated measures, adjusting for treatment group, sex, and main effects of age and additive genotype. RESULTS: Increasing age was associated with decreased BDR (−0.24 % per year). Polymorphisms rs295137 near SPATS2L and rs2626393 near ASB3 demonstrated their strongest associations with BDR in early childhood through adolescence, with a large decrease in their magnitude of effect from adolescence onward. The effect estimate for % BDR associated with rs295137 genotype (Beta=1.3; 95% CI 0.6 to 2.1) was diminished by age (interaction term=−0.06, p=0.004). The effect estimate for rs2626393 (Beta=−0.92 (95% CI −1.7 to −0.2) was also modified by age (interaction term= 0.05, p = 0.0004). CONCLUSIONS: Polymorphisms associated with BDR in childhood may not be relevant for predicting adolescent and adult BDR, which could reflect age-related changes in asthma phenotypes. TRIAL REGISTRATION: This work uses data from the previous clinical trial of asthma, the Childhood Asthma Management Program (CAMP), registered at ClinicalTrials.gov, #

Objectives This is the first review to identify, summarise and critically evaluate studies that examined psychological mediators of the relationship between childhood adversities and psychosis. Methods A database search (PsychINFO, MEDLINE, Web of Science, CINAHL) was conducted to identify eligible studies published between January 1980 and September 2017. A narrative synthesis and appraisal of methodological quality and statistical appropriateness of the primary studies was conducted. Results We identified 37 papers, comprising 9057participants with psychotic disorders and 63,059 non-clinical participants. Despite great variation in the mediators considered and the methodological and analytic quality of the primary studies, our synthesis suggests that the relationship between childhood adversity and psychosis is mediated by several “families” of mediating variables including post-traumatic sequelae (e.g. dissociation, PTSD symptoms), affective dysfunction and dysregulation, and maladaptive cognitive factors (e.g. self-esteem and beliefs and concepts about the self and others). More tentative evidence was observed for the role played by appraisals of subsequent circumstantial factors (e.g. “life hassles”). Substance misuse was not found to be a prominent mediator of the relationship between childhood adversity and psychotic experiences, but further high quality corroborative studies are required. Conclusions The importance of the five different (but not independent or mutually exclusive) families of mediators considered by the present evidence synthesis should be examined by future research employing appropriate modelling methods to better disentangle the contribution of these different processes. Nonetheless, they represent potentially valuable intervention targets that clinicians should consider whilst developing treatment plans for trauma survivors with distressing psychotic symptoms.

Background Mediation analysis tests whether the relationship between two variables is explained by a third intermediate variable. We sought to describe the usage and reporting of mediation analysis with time-to-event outcomes in published healthcare research. Methods A systematic search of Medline, Embase, and Web of Science was executed in December 2016 to identify applications of mediation analysis to healthcare research involving a clinically relevant time-to-event outcome. We summarized usage over time and reporting of important methodological characteristics. Results We included 149 primary studies, published from 1997 to 2016. Most studies were published after 2011 (n = 110, 74%), and the annual number of studies nearly doubled in the last year (from n = 21 to n = 40). A traditional approach (causal steps or change in coefficient) was most commonly taken (n = 87, 58%), and the majority of studies (n = 114, 77%) used a Cox Proportional Hazards regression for the outcome. Few studies (n = 52, 35%) mentioned any of the assumptions or limitations fundamental to a causal interpretation of mediation analysis. Conclusion There is increasing use of mediation analysis with time-to-event outcomes. Current usage is limited by reliance on traditional methods and the Cox Proportional Hazards model, as well as low rates of reporting of underlying assumptions. There is a need for formal criteria to aid authors, reviewers, and readers reporting or appraising such studies. Electronic supplementary material The online version of this article (10.1186/s12874-018-0578-7) contains supplementary material, which is available to authorized users.

Background Observation and feedback are core strategies of hand hygiene (HH) improvement. Direct overt observation is currently the gold standard method. Observation bias, also known as the Hawthorne effect, is a major disadvantage of this method. Our aim was to examine the variation of the Hawthorne effect on HH observation in different healthcare groups and settings. Methods A prospective cohort study was performed in a tertiary teaching hospital during a 15-month period. Up to 38 overt observers (82% nurses) and 93 covert observers (81% medical students) participated in HH observation. The HH events observed overtly were matched for occupation, department, observation time, and location with those observed covertly. The data of matched pairs were then analysed to detect possible Hawthorne effects on different variables. Results A total of 31,522 HH opportunities were observed (4581 overtly, 26,941 covertly). There were 3047 matched pairs after 1:1 matching of overt and covert observations. The overall HH compliance was higher with overt observation than with covert observation (78% vs. 55%, p

Although direct human observation of hand hygiene (HH) is considered the gold standard for measuring HH compliance, its accuracy is challenged by the Hawthorne effect.To compare HH compliance using both overt and covert methods of direct observation in different professional categories, hospital settings, and HH indications.A cross-sectional study was conducted in 28 units at King Abdulaziz Medical City, Riyadh, Saudi Arabia, between October 2012 and July 2013. Compliance was defined as performing handrubbing or handwashing during 1 of the World Health Organization 5 Moments for HH indications (ie, opportunities). Overt observation was done by infection preventionists (IPs) who were doing their routine HH observation. Covert observation was done by unrecognized temporarily hired professionally trained observers.A total of 15,883 opportunities were observed using overt observation and 7,040 opportunities were observed using covert observation. Overall HH compliance was 87.1% versus 44.9% using overt/covert observations, respectively (risk ratio, 1.94; P .001). The significant overestimation was seen across all professional categories, hospital settings, and HH indications.There is a considerable difference in HH compliance being observed overtly and covertly in all categories. More work is required to improve the methodology of direct observation to minimize the influence of the Hawthorne effect.